Analysis of molecular pathogenesis of thrombosis in Japanese using mice with genetic mutations in anticoagulation/fibrinolytic factors
Project/Area Number |
25461465
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Hematology
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Research Institution | National Cardiovascular Center Research Institute |
Principal Investigator |
Banno Fumiaki 国立研究開発法人国立循環器病研究センター, 研究所, 上級研究員 (00373514)
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Co-Investigator(Kenkyū-buntansha) |
AKIYAMA MASASHI 国立研究開発法人国立循環器病研究センター, 研究所, 室長 (30298179)
MIYATA TOSHIYUKI 国立研究開発法人国立循環器病研究センター, 病院, シニア研究員 (90183970)
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Project Period (FY) |
2013-04-01 – 2016-03-31
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Project Status |
Completed (Fiscal Year 2015)
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Budget Amount *help |
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2015: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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Keywords | プロテインS / プラスミノーゲン / ノックインマウス / 遺伝子変異 / 日本人の血栓症 |
Outline of Final Research Achievements |
The K196E mutation in protein S (PS) is a genetic risk factor for venous thromboembolism (VTE) with a prevalence of ~2% within the Japanese population. The A620T mutation in plasminogen (Plg), originally identified in a VTE patient, is present in ~4% of the Japanese population. We generated PS-K196E mice, PS-deficient mice and Plg-A622T mice. In this study, we analyzed their venous thrombotic states, comparing with mice carrying the factor V (FV) R504Q mutation, a genetic risk for VTE in Caucasians. A deep vein thrombosis model and two pulmonary embolism model experiments revealed that PS-K196E mice, PS-deficient mice and FV-R504Q mice were much more susceptible to VTE compared with wild-type mice, supporting a causal relationship between the PS-K196E mutation and VTE. However, experimental models of VTE showed largely similar phenotypes in Plg-A622T mice and wild-type mice. Hence, our results showed that the Plg-A620T mutation does not increase the risk of VTE.
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Report
(4 results)
Research Products
(31 results)
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[Journal Article] Contribution of ADAMTS13 to the better cell engraftment efficacy in mouse model of bone marrow transplantation2014
Author(s)
Matsui H, Takeda M, Soejima K, Matsunari Y, Kasuda S, Ono S, Nishio K, Shima M, Banno F, Miyata T, Sugimoto M
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Journal Title
Haematologica
Volume: 99
Issue: 10
Pages: 211-213
DOI
Related Report
Peer Reviewed / Open Access
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[Presentation] αIIbβ3活性化変異、αIIb(R990W)KIマウスは巨大血小板減少症とともに血小板機能障害をきたす2015
Author(s)
柏木浩和, 清水一亘, 國島伸治, 坂野史明, 加藤恒, 森川陽一郎, 田所誠司, 小亀浩市, 本田繁則, 宮田敏行, 金倉譲, 冨山佳昭
Organizer
第37回日本血栓止血学会学術集会
Place of Presentation
甲府市総合市民会館(甲府市)
Year and Date
2015-05-21
Related Report
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[Presentation] GT-like phenotype with macrothrombocytopenia induced by αIIbβ3 activating mutation in mice2014
Author(s)
Kiyomizu K, Kashiwagi H, Kunishima H, Banno F, Morikawa Y, Kato H, Tadokoro S, Kokame K, Honda S, Miyata T, Kanakura Y, Tomiyama Y
Organizer
第76回日本血液学会学術集会
Place of Presentation
大阪国際会議場(大阪市)
Year and Date
2014-11-02
Related Report
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[Presentation] インテグリンαIIbβ3活性化変異、αIIb(R990W)ノックインマウスの解析2014
Author(s)
清水一亘, 柏木浩和, 森川陽一郎, 加藤恒, 田所誠司, 坂野史明, 小亀浩市, 本田繁則, 金倉譲, 宮田敏行, 冨山佳昭
Organizer
第36回日本血栓止血学会学術集会
Place of Presentation
大阪国際交流センター(大阪市)
Year and Date
2014-05-31
Related Report
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[Presentation] マウス急性心筋梗塞モデルにおけるADAMTS13の心筋保護作用
Author(s)
土井政明, 松井英人, 竹田征治, 斎藤能彦, 武田麻衣子, 松成泰典, 西尾健治, 嶋緑倫, 坂野史明, 秋山正志, 小亀浩市, 宮田敏行, 杉本充彦
Organizer
第35回日本血栓止血学会学術集会
Place of Presentation
山形国際ホテル(山形市)
Related Report
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[Presentation] マウス骨髄移植モデルにおけるADAMTS13の移植ドナー細胞生着促進効果
Author(s)
松井英人, 土井政明, 武田麻衣子, 松成泰典, 西尾健治, 嶋緑倫, 副島見事, 粕田承吾, 坂野史明, 宮田敏行, 杉本充彦
Organizer
第35回日本血栓止血学会学術集会
Place of Presentation
山形国際ホテル(山形市)
Related Report
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[Presentation] ADAMTS13 accelerates the cell engraftment efficacy in mouse model of bone marrow transplantation
Author(s)
Matsui H, Doi M, Matsunari Y, Takeda M, Nishio K, Shima M, Soejima K, Banno F, Miyata T, Sugimoto M
Organizer
The International Society on Thrombosis and Haemostasis XXIV Congress
Place of Presentation
Amsterdam RAI(Amsterdam, Netherlands)
Related Report
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